Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report Date:
1965

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
BASF-Test, according to Hill, Ass. Food and Drug Off. 18, 1954.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): "Aethylenimin rein";
- Physical state: liquid;
- Analytical purity: pure.

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- No details reported.

ENVIRONMENTAL CONDITIONS
- not reported.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Undiluted in different amounts.
Details on dermal exposure:
TEST SITE
- Area of exposure ca. 5.7 cm² (0.2 mL/kg b.w.); ca. 3-4 cm² (0.1; 0.08; 0.04 mL/kg b.w.); ca. 2-3 cm² (0.02 mL/kg b.w.); ca. 1 cm² (0.01 mL/kg b.w.).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2; 0.1; 0.08; 0.04; 0.02; 0.01 mL/kg b.w.

Duration of exposure:
not reported.
Doses:
8.3; 16.6; 33.2; 66.4; 83 and 166 mg/kg b.w. calculated using the density of 0.83 g/cm³ at 24°C, corresponding to 0.01; 0.02; 0.04; 0.08; 0.1 and 0.2 mL/kg b.w.
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 4 - 5 weeks.
- Frequency of observations and weighing: Weighing was performed only at the beginning of the study for dose calculation. Observation of clinical signs was performed several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes.
Statistics:
No statistics were performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 12.45 mg/kg bw
Mortality:
Application of 66.4, 83.0 and 166.0 mg/kg b.w.: All rats perished after 1 day (166.0 mg/kg b.w.), after 2 - 5 days (83.0 mg/kg b.w.) or after 2 - 6 days (66.4 mg/kg b.w.).
Application of 33.2 mg/kg b.w.: 14 rats perished 3 - 11 days after application. The surviving animals were sacrificed after 5 weeks.
For summary see table below.
Clinical signs:
Application of 66.4, 83.0 and 166.0 mg/kg b.w.: Immediately after application hyperexcitability and after 2 hours apathy was observed.
Application of 33.2 mg/kg b.w.: These animals showed transient apathy and recovered within 24 hours.
Application of 8.3 and 16.6 mg/kg b.w.: 6 days after application apathy, food dislike and reduction in body weight were observed.
Body weight:
Not reported.
Gross pathology:
Application of 66.4, 83.0 and 166.0 mg/kg b.w.: Animals showed congestion in the renal medulla. Renal papillary necrosis occurred only in those animals that were treated with 66.4 and 83.0 mg/kg b.w. and died within 2-6 days.
Application of 33.2 mg/kg b.w.: Animals had renal papillary necrosis. The animals that were sacrificed after 5 weeks exhibited indications of healing processes.
Application of 8.3 and 16.6 mg/kg b.w.: Perished animals showed renal papillary necrosis. Regarding the animals that were sacrificed after 4 weeks, 4 of 7 animals that were treated with 16.6 mg/kg b.w. and 6 of 15 animals that were treated with 8.3 mg/kg b.w. showed no signs of nephropathy.

Any other information on results incl. tables

Dose

Animals

Exitus

Pathological, histological findings in the kidney

mL/kg b.w.

N

N

Within (days)

 

0.2

20

20

1

Congestion of medulla renalis

0.1

20

20

2-5

Congestion of medulla renalis

0.08

20

20

2-6

Congestion of medulla renalis , necrosis of renal papillae

0.04

20

14

3-11

necrosis of renal papillae

0.02

20

13

6-17

necrosis of renal papillae

0.01

20

5

12-13

necrosis of renal papillae

N= number of animals.

Value not calculated in the study. Cited in Zeller et al., 1970. Probably calculated using the data from this study.

Applicant's summary and conclusion